What makes cardiometabolic syndrome different in men versus women?


Cardiometabolic diseases (CMD) are complex diseases, exposing a huge burden on public health and remaining the leading cause of death worldwide. CMD incidence and clinical manifestation show substantial differences between men and women, which highlights the need for sex-specific strategies for CMD prevention and treatment. The mechanism underlying sex-difference may involve sex-specific effects of genetic factors, environmental factors and their interactions. However, no large-scale systematic analysis of these factors has been done in humans.
The primary aim of this study is to understand the molecular mechanisms behind sex-specific risk of CMD with the ultimate goal of better, sex-tailored prevention and treatment. To this end, I will apply a systems genetics approach to well-powered and well-phenotyped cohorts totaling 620,000 individuals from three large population-based studies: 60,000 individuals from the prospective LifeLines cohort study, 60,000 from the Estonian Biobank and 500,000 from the UK Biobank. Both genetic information and a wide range of environmental factors have been collected for these individuals.
The project aims will be achieved through three objectives. First, I will identify the sex-dependent genetic and environmental factors, and their interactions, that affect CMD and related phenotypes. Next, I will integrate these sex-dependent factors with intermediate omics phenotypes (such as gene expression, serum proteomics and metabolomics) to highlight the molecular pathways underlying sex differences. I also will profile sex-specific changes in intermediate phenotypes with age in order to understand the differential effect of ageing in men and women. Finally, I will apply machine learning approaches to construct sex-tailored risk models that can aid early prediction of CMD and which in future may assist diagnosis and personalized treatment.
This study will further our understanding of observed sex differences in CMD and related metabolic phenotypes and will be the first step toward sex-tailored disease prevention and treatment strategies.


Project number


Main applicant

Dr. D.V. Zhernakova

Affiliated with

Rijksuniversiteit Groningen, Universitair Medisch Centrum Groningen


01/01/2020 to 01/01/2023